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Original Articles

Hypoglycemia Overrides Amylin-Mediated Regulation of Gastric Emptying in Rats

  1. Bronislava R Gedulin and
  2. Andrew A Young
  1. Amylin Pharmaceuticals San Diego, California
  1. Address correspondence and reprint requests to Dr. Andrew A. Young, Amylin Pharmaceuticals, 9373 Towne Centre Dr., San Diego, CA 92121. Email: ayoung{at}amylin.com
Diabetes 1998 Jan; 47(1): 93-97. https://doi.org/10.2337/diab.47.1.93
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Abstract

Amylin, a 37-amino acid peptide hormone co-secreted with insulin, potently governs the rate of gastric emptying. Hypoglycemia, in the absence of agents such as amylin, is reported to accelerate gastric emptying. We asked whether hypoglycemia had a similar action on gastric emptying in the presence of amylin. In preliminary experiments using a phenol red gavage technique in fasted SD rats, we showed that insulin administration accelerated gastric emptying in a dosage-dependent manner. This acceleration was totally prevented by coadministration of glucose in dosages that prevented a change in plasma glucose, indicating that insulin per se did not affect gastric emptying. The effect on gastric emptying of hypoglycemia induced by a 5 mU/min insulin infusion (t = 5–90 min) was assessed in conscious rats continuously infused with amylin (50 pmol · kg−1 · min−1; t = −30 to 90 min). Gastric emptying was indicated by the appearance in plasma of label from 3-O-methyl-[3H]glucose gavaged at t = 0 min. Label appearance was markedly inhibited in rats preinfused with amylin (84% reduced vs. saline controls at t = 30min), indicating amylin inhibition of gastric emptying. In amylin-treated rats that were subsequently infused with insulin, gavaged label abruptly appeared in plasma when plasma glucose had fallen to 2.1 ± 0.1 mmol/1 (at t ≅ 45 min), consistent with a reversal by hypoglycemia of amylin's inhibition of gastric emptying. These data support the idea of a central “fail-safe” mechanism whereby hypoglycemia can override the slowing of gastric emptying by amylin.

  • Received July 1, 1996.
  • Revision received September 9, 1997.
  • Accepted September 9, 1997.
  • Copyright © 1998 by the American Diabetes Association

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January 1998, 47(1)
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Hypoglycemia Overrides Amylin-Mediated Regulation of Gastric Emptying in Rats
Bronislava R Gedulin, Andrew A Young
Diabetes Jan 1998, 47 (1) 93-97; DOI: 10.2337/diab.47.1.93

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Hypoglycemia Overrides Amylin-Mediated Regulation of Gastric Emptying in Rats
Bronislava R Gedulin, Andrew A Young
Diabetes Jan 1998, 47 (1) 93-97; DOI: 10.2337/diab.47.1.93
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